Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 12 July 2005
Vol. 2005, Issue 292, p. pe35
[DOI: 10.1126/stke.2922005pe35]


β-Catenin, Cancer, and G Proteins: Not Just for Frizzleds Anymore

Craig C. Malbon*

Department of Pharmacology, School of Medicine, Health Sciences Center, SUNY–Stony Brook, Stony Brook, NY 11794–8651, USA.

Abstract: The lipid metabolite lysophosphatidic acid (LPA) mediates an impressive set of responses that includes morphogenesis, cell proliferation, cell survival, cell adhesion, and cell migration. LPA exerts its downstream signaling by binding to the LPA1, LPA2, and LPA3 (formerly Edg-2, -4, and -7) family of seven-transmembrane, segmented, heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors. LPA actions of therapeutic interest include effects on wound healing, atherogenesis, thrombogenesis, and, of course, cancer. LPA has been implicated in the progression of human breast, ovarian, prostate, head and neck, and colon malignancies. In view of these earlier observations, a recent report that LPA stimulates the proliferation of colon cancer–derived cell lines was greeted with great anticipation for its possible contribution to the unraveling of details of cancer signaling downstream of LPA. LPA was shown to stimulate nuclear accumulation of β-catenin in a manner that depended on activation of Gαq by LPA2,3, activation of phospholipase Cβ, activation of a conventional protein kinase C, and phosphorylation and inhibition of glycogen synthase kinase 3-β. The phosphorylation of β-catenin by this kinase marks the protein for intracellular degradation; LPA suppresses this degradation and stimulates β-catenin accumulation. β-catenin is a pivotal molecule in the control of cell cycle progression and gene expression, activating both processes in combination with lymphoid-enhancing factor/T cell–factor–sensitive transcription and inhibiting both processes in combination with FOXO transcription factors. The ability of LPA to increase the cytoplasmic and nuclear accumulation of β-catenin provides a new dimension of knowledge linking lipid mediators to the dysregulation of β-catenin signaling in cancer.

*Contact information. e-mail, craig{at}

Citation: C. C. Malbon, β-Catenin, Cancer, and G Proteins: Not Just for Frizzleds Anymore. Sci. STKE 2005, pe35 (2005).

Read the Full Text

Wnt3a-stimulated LRP6 phosphorylation is dependent upon arginine methylation of G3BP2.
R. K. Bikkavilli and C. C. Malbon (2012)
J. Cell Sci. 125, 2446-2456
   Abstract »    Full Text »    PDF »
Protease-activated Receptor-1 (PAR1) Acts via a Novel G{alpha}13-Dishevelled Axis to Stabilize {beta}-Catenin Levels.
H. Turm, M. Maoz, V. Katz, Y. J. Yin, S. Offermanns, and R. Bar-Shavit (2010)
J. Biol. Chem. 285, 15137-15148
   Abstract »    Full Text »    PDF »
Dishevelled-KSRP complex regulates Wnt signaling through post-transcriptional stabilization of {beta}-catenin mRNA.
R. K. Bikkavilli and C. C. Malbon (2010)
J. Cell Sci. 123, 1352-1362
   Abstract »    Full Text »    PDF »
Targeting mediators of Wnt signalling pathways by GnRH in gonadotropes.
S. Gardner, E. Stavrou, P. E Rischitor, E. Faccenda, and A. J Pawson (2010)
J. Mol. Endocrinol. 44, 195-201
   Abstract »    Full Text »    PDF »
Bryostatin 1 modulates {beta}-catenin subcellular localization and transcription activity through protein kinase D1 activation.
M. Jaggi, S. C. Chauhan, C. Du, and K.C. Balaji (2008)
Mol. Cancer Ther. 7, 2703-2712
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882